Trial Outcomes & Findings for Anti-Cytokine Therapy for Hemodialysis InflammatION (NCT NCT03141983)

NCT ID: NCT03141983

Last Updated: 2023-03-14

Results Overview

The primary safety endpoint is serious adverse events per patient-year.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 80 participants
• Primary outcome timeframe: 48 Weeks (after the 24-week treatment period and the 24-week post-treatment period)
• Results posted on: 2023-03-14

Participant Flow

Participant milestones

Measure	Anakinra Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Overall Study STARTED	38	42
Overall Study COMPLETED	30	34
Overall Study NOT COMPLETED	8	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Anti-Cytokine Therapy for Hemodialysis InflammatION

Baseline characteristics by cohort

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.	Total n=80 Participants Total of all reporting groups
Age, Continuous	59.6 years STANDARD_DEVIATION 10.0 • n=5 Participants	54.1 years STANDARD_DEVIATION 13.5 • n=7 Participants	56.7 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	24 Participants n=7 Participants	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	39 Participants n=7 Participants	72 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
hsCRP, mg/L	7.2 mg/L n=5 Participants	7.2 mg/L n=7 Participants	7.2 mg/L n=5 Participants

PRIMARY outcome

Timeframe: 48 Weeks (after the 24-week treatment period and the 24-week post-treatment period)

The primary safety endpoint is serious adverse events per patient-year.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis	2.71 events per patient-year	2.74 events per patient-year

PRIMARY outcome

Timeframe: Change from Baseline to 24 Weeks (end of treatment phase)

For this outcome, CRP measurements from Baseline and Week 24 were compared.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Log-transformed Circulating CRP Concentration After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis	-0.4 Log (mg/L) Standard Deviation 0.9	-0.2 Log (mg/L) Standard Deviation 0.7

SECONDARY outcome

Timeframe: 24-week treatment period

Adverse events were one measure used to assess safety and tolerability of anakinra, for patients receiving maintenance hemodialysis. This measure assessed the number of participants with adverse events that precluded further treatment with the study agent.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Number of Participants With Adverse Events That Preclude Further Treatment With the Study Agent	3 Participants	1 Participants

SECONDARY outcome

Timeframe: 48 weeks

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Infections	5 Participants	11 Participants

SECONDARY outcome

Timeframe: 48 weeks

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Neutropenia	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 48 weeks

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Thrombocytopenia	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 48 weeks

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Systemic Hypersensitivity Reactions	1 Participants	0 Participants

SECONDARY outcome

Timeframe: change after 24 weeks of treatment

Change in circulating markers of inflammation and oxidative stress between baseline and end of treatment

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Markers of Inflammation and Oxidative Stress - IL-1β pg/ml	0.0 pg/ml Interval 0.0 to 0.1	0.0 pg/ml Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: change after 24 weeks of treatment

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Markers of Inflammation and Oxidative Stress - IL-6, pg/mL	-0.7 pg/mL Interval -2.4 to -0.3	0.0 pg/mL Interval -1.0 to 0.7

SECONDARY outcome

Timeframe: change after 24 weeks of treatment

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Markers of Inflammation and Oxidative Stress - IL-10, pg/mL	0.0 pg/mL Interval -0.1 to 0.1	0.0 pg/mL Interval -0.1 to 0.1

SECONDARY outcome

Timeframe: change after 24 weeks of treatment

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Markers of Inflammation and Oxidative Stress - TNF Alpha, pg/ml	-0.2 pg/ml Interval -1.0 to 0.1	0.0 pg/ml Interval -0.3 to 0.7

SECONDARY outcome

Timeframe: change after 24 weeks of treatment

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Markers of Inflammation and Oxidative Stress - Albumin, g/dL	0.0 g/dL Interval -0.2 to 0.1	0.0 g/dL Interval -0.2 to 0.2

SECONDARY outcome

Timeframe: 24 Weeks (end of treatment phase)

Change in patient reported outcomes using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale from Baseline to Week 24.

To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.

All participants were assessed with the same scoring system.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Patient-reported Indicators of Fatigue After 24 Weeks of Treatment	-4.9 score on a scale Standard Deviation 12.1	-0.4 score on a scale Standard Deviation 8.7

SECONDARY outcome

Timeframe: 24 Weeks (end of treatment phase)

Change in patient reported outcomes using the Beck Depression Inventory - II (BDI-II) scale at baseline, Weeks 12, 24 and 28.

The instrument uses a 21-item self-report inventory measuring the severity of depression in adolescents and adults.The standard cut-offs are as follows: 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Patient-reported Indicators of Depression After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis	-0.9 score on a scale Standard Deviation 5.7	-0.1 score on a scale Standard Deviation 7.5

SECONDARY outcome

Timeframe: Change after 24 weeks of treatment

Mean change in patient reported outcomes using the Dialysis Symptom Index, Burden subscale

The DSI is a 30-question instrument assessing whether participants report a particular symptom during the past week and the severity of that symptom. Symptom burden is assessed using 30 "yes/no" questions. The scale is a count of the number of "yes" responses. The minimum is 0. The maximum is 30. The mean change in score after 24 weeks of treatment was measured. A lower score is better as a higher score indicates greater symptom burden.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Burden of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis	0.2 score on a scale Standard Deviation 5.6	0.3 score on a scale Standard Deviation 3.8

SECONDARY outcome

Timeframe: Change after 24 weeks of treatment

Change in patient reported outcomes using the Dialysis Symptom Index, Severity subscale

The DSI severity subscale includes 30-questions assessing whether a symptom is present (previous outcome - burden subscale). The severity of each symptom that was reported as being present was assessed by asking patients to rate the degree to which the symptom was bothersome using a five-point Likert scale (1 = "not at all bothersome" to 5 = "bothers very much"). Higher scores indicating greater symptom severity. The minimum score is 30, the maximum score is 150. The mean change was used to measure this outcome.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Severity of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis	-4.0 score on a scale Standard Deviation 24.4	-0.3 score on a scale Standard Deviation 15.1

SECONDARY outcome

Timeframe: 24 Weeks (end of treatment phase)

Change in patient reported outcomes using the Kidney Disease - Quality of Life subscale of the SF-12 (KDQOL SF-12) at baseline, Weeks 12, 24 and 28.

A higher score reflects a more favorable health state. The questionnaire consists of 24 questions and the total possible score sum is 0-100. Items in the same scale are averaged to create scale scores.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Patient-reported Indicators of Quality of Life After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis	-3.5 score on a scale Standard Deviation 21.5	-3.3 score on a scale Standard Deviation 14.2

SECONDARY outcome

Timeframe: 24 Weeks (end of treatment phase)

Change in measurement of hand grip strength using a standard dynamometer at baseline, Weeks 12, 24 and 28. This was measured in kg using the dominant hand.

Outcome measures

Measure	Anakinra n=38 Participants Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 Participants Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Change in Measure of Muscle Strength (Hand Grip Strength) After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis	-0.5 kilograms Standard Deviation 4.1	-0.4 kilograms Standard Deviation 3.9

Adverse Events

Anakinra

Serious events: 17 serious events

Other events: 7 other events

Deaths: 2 deaths

Placebo

Serious events: 23 serious events

Other events: 11 other events

Deaths: 4 deaths

Serious adverse events

Measure	Anakinra n=38 participants at risk Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 participants at risk Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Vascular disorders hypotension	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Infections and infestations Bacteremia	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Vascular disorders Vascular Access Complication	7.9% 3/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Injury, poisoning and procedural complications Fall	2.6% 1/38 • 48 Weeks	4.8% 2/42 • 48 Weeks
Metabolism and nutrition disorders hypoglycemia	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Infections and infestations Osteomyelitis	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Psychiatric disorders Suicidal Ideation	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Surgical and medical procedures Kidney transplant	2.6% 1/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Nervous system disorders Severe central canal stenosis	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Gastrointestinal disorders Gastrointestinal bleeding	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Gastrointestinal disorders Abdominal pain	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Cardiac disorders Chest pain	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Gastrointestinal disorders Anal fissure	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Infections and infestations Pneumonia	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Cardiac disorders Atrial Fibrillation	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Respiratory, thoracic and mediastinal disorders Bronchiolitis	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Vascular disorders Clotted AVF	0.00% 0/38 • 48 Weeks	7.1% 3/42 • 48 Weeks
Vascular disorders Thrombolysis	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Cardiac disorders Sudden cardiac death	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Eye disorders Epiretinal membrane	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Cardiac disorders non-ST elevated myocardial infarction	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Cardiac disorders Cardiac catheterization	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Respiratory, thoracic and mediastinal disorders acute hypoxic respiratory failure	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Nervous system disorders autonomic dysfunction	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Injury, poisoning and procedural complications Wound complication	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Gastrointestinal disorders Gastroparesis	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/38 • 48 Weeks	4.8% 2/42 • 48 Weeks
Metabolism and nutrition disorders hyperkalemia	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Gastrointestinal disorders Norovirus associated gastroenteritis	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Infections and infestations COVID19	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks

Other adverse events

Measure	Anakinra n=38 participants at risk Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP. Anakinra: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.	Placebo n=42 participants at risk Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Placebo: Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Infections and infestations Sinusitis	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Infections and infestations COVID	2.6% 1/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Blood and lymphatic system disorders neutropenia	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Infections and infestations Flu	2.6% 1/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Immune system disorders Urticaria	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Respiratory, thoracic and mediastinal disorders Sinus congestion	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Infections and infestations Bacteremia	2.6% 1/38 • 48 Weeks	0.00% 0/42 • 48 Weeks
Infections and infestations Upper respiratory infection	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Infections and infestations Acute osteomyelitis of left foot	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Infections and infestations Pneumonia	0.00% 0/38 • 48 Weeks	4.8% 2/42 • 48 Weeks
Infections and infestations Norovirus	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Infections and infestations Non-serious infection	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Infections and infestations Bronchitis	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Infections and infestations Pyelonephritis of transplanted kidney	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks
Infections and infestations Toe blisters	0.00% 0/38 • 48 Weeks	2.4% 1/42 • 48 Weeks

Additional Information

Natalie Kuzla

University of Pennsylvania

Phone: 2672524208

Email: nkuzla@pennmedicine.upenn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place